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Genetic association and interaction between the IRF5 and TYK2 genes and systemic lupus erythematosus in the Han Chinese population

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Abstract

Objectives

The purpose of this case–control study was to investigate whether polymorphisms and gene–gene interactions of the two type I interferon (IFN) genes (IRF5 and TYK2) are the susceptible factors of systemic Lupus erythematosus (SLE) in the Han Chinese population.

Methods

The four variants [rs2004640, rs2070197, rs10954213 and exon6 insertion/deletion (in/de)] of IRF5 gene and five single-nucleotide polymorphisms (SNPs) (rs280500, rs280519, rs2304256, rs8108236, rs12720270) of TYK2 gene were examined in a cohort of 642 SLE patients and 642 healthy controls. Genotyping was conducted using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) and confirmed by direct sequencing in 10 % sample randomly.

Results

Rs2070197 was not polymorphic in this study, and was excluded in further analysis. Significant association was found for loci on IRF5 (rs2004640: p = 0.0003, p corr  = 0.0012) and TYK2 (rs280500: p = 8.83 × 10−6, p corr  = 4.41 × 10−5; rs2304256: p = 3.71 × 10−6, p corr  = 1.85 × 10−5; rs8108236: p = 0.0004, p corr  = 0.002), but not for other SNPs. Significant association was also observed for genotypes of IRF5 (rs2004640, p = 0.0009, p corr  = 0.0036) and TYK2 SNPs (rs280500: p = 5.21 × 10−5, p corr  = 2.61 × 10−4; rs2304256: p = 7.72 × 10−6, p corr  = 3.86 × 10−5; rs8108236: p = 0.002, p corr  = 0.01). Nevertheless, two haplotypes based on the 3 variants [exon6(in/de), rs10954213, rs2004640] of IRF5 (DAG and IAT) could define protective or susceptibility haplotype in SLE. Similarly, three haplotypes containing 5 SNPs (rs280500, rs280519, rs2304256, rs8108236, rs12720270) of TYK2 (GATAT, AGGAT and GAGGT) may also be associated with SLE in Han Chinese. Additionally, the gene–gene interaction analysis was conducted on the IRF5 and TYK2 SNPs. And a three-way interaction between TYK2 rs280500, rs2304256 and IRF5 rs10954213 and SLE was found (p < 0.0001).

Conclusions

Genetic associations and gene–gene interactions of IRF5 and TYK2 were significantly detected in Han Chinese with SLE. Our results had important implications for future research on the role of type I IFN function in SLE susceptibility.

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Acknowledgments

We are grateful to the SLE and RA patients and control individuals for participating in this study. This study was supported by the Foundation for Young Professors of the Education Department of Hunan (15B0146), the construct program of the key discipline in Hunan province and the Fundamental Research Funds for the Central Universities (2015IVA048 and 2015IB004).

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    Authors and Affiliations

    1. Department of Human Anatomy, Histology and Embryology, Institute of Neuroscience, Changsha Medical University, Changsha, People’s Republic of China

      Liang Tang

    2. School of Basic Medical Science, Changsha Medical University, Changsha, 410219, People’s Republic of China

      Liang Tang & Yan Wang

    3. Department of Clinical Medicine, Second School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China

      Pengcheng Wan

    4. Department of Biological Science and Biotechnology, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, 430070, People’s Republic of China

      Yong Wang, Jiabao Pan & Bifeng Chen

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    Correspondence to Liang Tang or Bifeng Chen.

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    Responsible Editor: John Di Battista.

    L. Tang and P. Wan contributed equally to this work.

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    Tang, L., Wan, P., Wang, Y. et al. Genetic association and interaction between the IRF5 and TYK2 genes and systemic lupus erythematosus in the Han Chinese population. Inflamm. Res. 64, 817–824 (2015). https://doi.org/10.1007/s00011-015-0865-2

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